This invention relates to a leukocyte-removing material composed mainly of a hydrophobic polyolefin and a process for producing a hydrophilized polyolefin material suitable as said leukocyte-removing-material.
In recent years, various adverse side effects due to contamination with leukocytes have been known in the field of blood transfusion. For preventing the side effects, leukocytes are removed by using a material such as highly hydrophilic polyester nonwoven fabric or cotton fabric. In the transfusion of a platelet product, a technique of coating the surface of a leukocyte-removing material with a hydrophilic polymer or the like is employed for suppressing the adhesion of platelets to the leukocyte-removing material.
On the other hand, improvements have been made in techniques for selectively removing leukocytes for curing autoimmune diseases such as systemic lupus erythematosus, malignant rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn disease, leukemia, cancer, etc., or for immunosuppression before transplantation.
Materials such as highly hydrophilic polyester nonwoven fabric, cotton fabric, etc. have been widely used as leukocyte-removing materials because of their high leukocyte-removing capability. From the viewpoint of compatibility at the time of contact with blood, an ester structure or an amide structure is generally given to a leukocyte-removing material in order to impart hydrophilicity to the blood contact surface of the material. Such leukocyte-removing materials, however, are thermally unstable in the excess of attachment of importance to hydrophilicity. Particularly when the materials are subjected to wet heat sterilization or the like, their hydrolysis or the like is liable to take place. Thus, they are not always satisfactory as materials for medical supplies.
JP-A-3-27317 discloses a leukocyte-removing material obtained by grafting a monomer onto polyester fiber having a pore major axis of 0.5 to 4 xcexcm and a CWST (critical wet surface tension) of 55 to 80 dyne/cm, by means of a radiation. This material, however, is poor in thermal strength because the polyester fiber or the aforesaid monomer has ester linkages. Therefore, the grafted monomer is liable to be released by dissolution during wet heat sterilization.
On the other hand, polyolefins are materials having an excellent thermal stability and they can be said to be preferable as materials for medical supplies which should be sterilized by high energy, such as wet heat sterilization, because they retain their strength as the materials even after the sterilization. The polyolefins, however, have a CWST of approximately 25 dyne/cm-30 dyne/cm and hence it has been not suitable to utilize them as they are.
Therefore, JP-A-1-256971 discloses a leukocyte-removing material comprising polypropylene nonwoven fabric hydrophilized by plasma treatment. However, the plasma treatment can impart hydrophilicity to the material temporarily but the imparted hydrophilicity decreases with the lapse of time. Thus, the hydrophilicity cannot be stably retained for a long period of time. Such a leukocyte-removing material is used immediately after the hydrophilization in rare cases and hence should be kept hydrophilized for a certain period or permanently. Accordingly, the hydrophilization by the plasma treatment is not desirable. In addition, when the plasma treatment is carried out, a considerable amount of electric charge is produced for increasing the hydrophilicity, so that the possibility of complement activation and bradykinin production is increased. Thus, the material hydrophilized by the plasma treatment is not desirable as a material for treating blood.
In view of such problems, the present invention is intended to provide a leukocyte-removing material which is hardly decomposed even by wet heat sterilization and has a stable hydrophilicity, and to provide a material which can retain hydrophilicity permanently irrespective of the hydrophobicity of a raw material therefor, has good priming properties, and has an excellent ability to remove leukocytes selectively.
Furthermore, the present invention is intended to provide a process for producing a hydrophilized polyolefin which retains its hydrophilicity for a long period of time, without greatly changing characteristics of polyolefin.
The present inventors eanestly investigated in order to solve the problems described above, and consequently found that a leukocyte-removing material comprising a polyolefin and having a factor of hydrophilicity of less than 40% and not less than 30% is very effective. Moreover, the present inventors found that the above-mentioned leukocyte-removing material possesses greatly improved priming properties and is surprisingly stable to wet heat sterilization, whereby the present invention has been accomplished.
Thus, one aspect of the present invention is directed to a leukocyte-removing material composed substantially of a polyolefin and having a factor of hydrophilicity of less than 40% and not less than 30%.
Another aspect of the present invention is directed to a process for producing a hydrophilized polyolefin which comprises a step of irradiating substantially a polyolefin with a radiation in a dose of less than 300 kGy and not less than 15 kGy, and a step of heating said polyolefin at a temperature of lower than 125xc2x0 C. and not lower than 75xc2x0 C. after the irradiation with the radiation.
The term xe2x80x9cleukocyte-removing materialxe2x80x9d used herein means a material for removing leukocytes from a leukocyte-containing fluid such as blood or a body fluid by a mechanism such as filtration or adsorption.
In the leukocyte-removing material of the present invention, the term xe2x80x9ccomposed substantially of a polyolefinxe2x80x9d means that the leukocyte-removing material is composed essentially of a modified polyolefin obtained by imparting hydrophilicity to naturally hydrophobic polyolefin by modification. In detail, the term means that the leukocyte-removing material is composed of a product obtained by changing (modifying) a polyolefin itself, for example, by irradiation with a radiation without converting the polyolefin to another material.
Therefore, the leukocyte-removing material xe2x80x9ccomposed substantially of a polyolefinxe2x80x9d of the present invention does not include, for example, products obtained by grafting a hydrophilic monomer as another component onto a polyolefin, and products obtained by coating a polyolefin with a hydrophilic monomer as another component.
The leukocyte-removing material of the present invention may contain antioxidants and stabilizers, which are usually contained in polyolefins. In addition, the leukocyte-removing material of the present invention may contain a small amount of a hydrophobic polymer other than the polyolefin, for holding of the polyolefin.
The polyolefin refers to a polymer obtained by homopolymerization or copolymerization of one or more alkenes or alkynes. The polyolefin includes, for example, polyolefins obtained by homopolymerization, such as polyethylenes, polypropylenes, polybutylenes, etc., and polyolefins obtained by copolymerization, such as polypropylene-polyethylene copolymers, polybutylene-polypropylene copolymers, etc. From the viewpoint of thermal strength, the polypropylenes, polybutylenes, polyethylene-polypropylene copolymers, polyethylene-polybutylene copolymers, etc. are preferable. From the viewpoint of the controllability of the leukocyte-removing material, the polypropylenes, polypropylene-polyethylene copolymers, etc. are the most preferable.
The term xe2x80x9cfactor of hydrophilicityxe2x80x9d used herein is defined as follow: there are prepared aqueous ethanol solutions having predetermined and stepwise varied weight ratios of ethanol to water, a droplet (volume: about 10xcexcL) of each of the solutions is brought into contact with a leukocyte-removing material, starting from the lowest concentration, and a concentration of the aqueous ethanol solution at which said leukocyte-removing material is wetted for the first time is called the factor of hydrophilicity. However, depending on the material, the material is not completely wetted in some cases because the wetting is dependent on the density of the material. In this case, the factor of hydrophilicity referred to herein is defined as a concentration of the aqueous ethanol solution at which the contact angle becomes 120xc2x0 or more. The term xe2x80x9ccontact anglexe2x80x9d used here means an angle between the droplet and said leukocyte-removing material. When the contact angle is measured on the spherical surface or cylindrical surface of a fiber or the like, it is defined as an angle made by the droplet outer surface and a tangent between the material surface and the center of the droplet. That is, the contact angle is defined as an angle made by the droplet and a tangent to the material which touches the material surface at the center of the droplet on the portion on which the droplet is in contact with the material. The contact angle can be measured with a well-known contact angle measuring apparatus.
The factor of hydrophilicity of each fibrous material measured by this method is 43% for polyethylene nonwoven fabric, 41% for polypropylene nonwoven fabric and 43% for polybutylene fiber. All polyolefin fibers having a usual composition have a factor of hydrophilicity of more than 40%.
The leukocyte-removing material of the present invention should be weakly hydrophilic to such an extent that the factor of hydrophilicity is less than 40% and not less than 30%, from the viewpoint of priming properties, affinity for blood, and low stimulating properties for blood.
When the factor of hydrophilicity of the material is 40% or more, the material has a high hydrophobicity and a low affinity for plasma, so that it repels blood. Therefore, such a material is not suitable. In addition, when the factor of hydrophilicity of the material is 40% or more, the material cannot be primed with water unless it is pretreated with a solution having a relatively high affinity for the material, such as ethanol. Therefore, troublesome operations are required for priming. Thus, such a material is not suitable.
On the other hand, when the factor of hydrophilicity is less than 30%, the material is increased in hydrophilicity, so that its priming properties are improved. But, the presence of hydrophilic groups increases the possibility of the activation of a large amount of complements and the production of bradykinin during blood treatment. Therefore, such a material is also not suitable.
Polyolefin materials having such a hydrophilicity imparted by irradiation with a radiation that the factor of hydrophilicity is less than 30% possess a deteriorated strength and hence are not suitable as materials for medical supplies for removing leukocytes.
The factor of hydrophilicity is preferably less than 40% and not less than 31%, more preferably less than 39% and not less than 32%.
A porous leukocyte-removing material composed substantially of a polyolefin and having the factor of hydrophilicity according to the present invention can be obtained by a method of giving, for example, hydroxyl groups and/or keto groups to a material having a factor of hydrophilicity of 40% or more, to adjust the factor of hydrophilicity to less than 40% and not less than 30%. Specifically, the factor of hydrophilicity of the leukocyte-removing material can be adjusted to a value in a desirable range by giving hydroxyl groups and/or keto groups by any of {circle around (1)} a method of hydrolyzing ester groups or ether groups naturally present in the material, {circle around (2)} a method of irradiating a polyolefin with a radiation in the presence of oxygen to form a peroxide surface, and {circle around (3)} a method of causing a chemical reaction by the use of an oxidizing agent such as sulfuric acid.
Of these, the method of irradiating a polyolefin having no hydroxyl group with a radiation in the presence of oxygen makes it possible to give hydroxyl groups and/or keto groups so as to attain a desirable factor of hydrophilicity, most satisfactorily and easily. When the irradiation with a radiation is carried out in air or in the presence of oxygen, a peroxide is produced in the material. Hydroxyl groups can be introduced onto the surface by cleaving radicals by pyrolizing this peroxide in the presence of water or subjecting the peroxide to redox decomposition with a reducing agent. Keto groups can also be efficiently introduced by the recombination of radicals which takes place simultaneously. As the radiation, electron beams are most preferably used from the viewpoint of, in particular, transmittance.
A leukocyte-removing material obtained by irradiating a polyolefin with a radiation in a dose of less than 300 kGy and not less than 15 kGy and heating the polyolefin at a temperature of lower than 125xc2x0 C. and not lower than 75xc2x0 C. after the irradiation is preferable from the viewpoint of, in particular, stability of hydrophilicity and biocompatibility.
When a slight amount of hydroxyl groups are given to a polyolefin, any of the well-known methods described above may be adopted, though it it preferable to give hydroxyl groups and/or keto groups by covalent binding.
The leukocyte-removing material of the present invention preferably has hydroxyl groups and/or keto groups on the material surface.
The word xe2x80x9csurfacexe2x80x9d used herein means a face which can come in contact with blood, and it does not include the inside of the material and internal faces, with which blood cannot come in contact. Therefore, whatever values the factor of hydrophilicity of such portions (the inside of the material and internal surfaces) may have, they need not be taken into consideration in determining the factor of hydrophilicity of the surface of the leukocyte-removing material of the present invention.
The leukocyte-removing material of the present invention preferably comprises, in particular, at least a polypropylene-polypropylene alcohol. The polypropylene-polypropylene alcohol may be either a copolymer of propylene and propylene alcohol, or a material obtained by giving hydroxyl groups to a polypropylene subsequently by covalent binding.
In the leukocyte-removing material of the present invention, a porous material having through-holes is effectively used as a raw material. Preferable examples of form of the porous material are a fibrous form, spongy form, foam, etc. Of materials of these forms, fibrous materials are particularly satisfactorily used as the leukocyte-removing material from the viewpoint of production and the leukocyte-removing capability of the final product. Preferable specific examples of form of the fibrous materials are a fibrous form, cotton form, thread form, bundle form, reed screen form, woven fabric form and nonwoven fabric form. Woven fabric and nonwoven fabric are preferable from the viewpoint of ease of controlling the material form, handleability and leukocyte-removing capability.
Nonwoven fabric is the most preferable from the viewpoint of ease of controlling performance characteristics.
The average pore size of the porous material is preferably less than 100 xcexcm and not less than 1.0 xcexcm. When the average pore size is less than 1.0 xcexcm, the fluidity of blood is undesirably low, namely, the resistance to flow is undesirably increased. On the other hand, when the average pore size is 100 xcexcm or more, the frequency of contact with leukocytes is undesirably decreased because of a decrease in the surface area, resulting in a decreased leukocyte removal rate. In view of the above, the average pore size of the porous material is more preferably less than 80 xcexcm and not less than 3 xcexcm, most preferably less than 60 xcexcm and not less than 5 xcexcm.
The term xe2x80x9caverage pore sizexe2x80x9d used herein means the diameter of pores determined by a mercury injection method. On the basis of values measured by the mercury injection method (Poresizer 9320, mfd. by Shimadzu Corp.), a graph is drawn by plotting pore volume on the axis of ordinate corresponding to individual pore sizes on the axis of abscissa, and the average pore size is defined as a value corresponding to the peak of the graph (a mode). As the values measured by the mercury injection method, values measured in a pressure range of 1 to 2650 psia are used.
In the present invention, when the form of the leukocyte-removing material is a nonwoven fabric form, the fiber diameter is preferably thin for increasing the frequency of contact with leukocytes. The average fiber diameter is preferably less than 100 xcexcm and not less than 1 xcexcm. From the viewpoint of leukocyte-removing properties, the average fiber diameter is more preferably less than 50 xcexcm and not less than 1 xcexcm, most preferably less than 30 xcexcm and not less than 1 xcexcm.
The average diameter of fibers constituting the nonwoven fabric is determined, for example, by taking scanning electron micrographs of the fibers constituting the nonwoven fabric, measuring the diameter of 100 or more of the fibers selected at random, and calculating the number average of the measured values.
In the leukocyte-removing material of the present invention, the basis weight of the nonwoven fabric can be measured by a well-known test method and is preferably as large as possible from the viewpoint of strength. Specifically, the basis weight is preferably 15 g/m2 or more. On the other hand, when the basis weight is too large, the flowability of blood is deteriorated. Therefore, the upper limit of the basis weight is preferably less than 200 g/m2. The basis weight of the nonwoven fabric is more preferably less than 150 g/m2 and not less than 20 g/m2, most preferably less than 100 g/m2 and not less than 20 g/m2.
As the nonwoven fabric used in the present invention, there may be used either a single nonwoven fabric or a material obtained by laminating two or more nonwoven fabrics different in basis weight or average fiber diameter.
The leukocyte-removing material of the present invention is especially excellent in biocompatibility and can suppress complement activation or bradykinin production. Therefore, the leukocyte-removing material of the present invention can be specified by its high biocompatibility.
The concentration of a complement activated by the contact of the leukocyte-removing material with blood is preferably low. The concentration of the activated complement is preferably less than 10 times and not less than 0.5 time as high as that before the contact. As an indication of the complement activation, there can be employed the concentration of an activated complement C3a or C4a, which is easily formed, and the biocompatibility can be satisfactorily evaluated by this indication. When the factor of hydrophilicity is less than 30%, a large amount of hydrophilic groups such as hydroxyl groups are present, so that the concentration of the activated complement is increased, namely, the biocompatibility is not high. Therefore, such a factor of hydrophilicity is not very desirable. Accordingly, the concentration of the activated complement is more preferably less than 8 times and not less than 0.5 time, most preferably less than 6 times and not less than 0.5 time, as high as that before the contact.
The concentration of the activated complement can be measured by a method such as a well-known radioimmunoassay with two antibodies [Nippon Rinsho (Japanese Clinic) Vol. 53, Special Number (the last volume) (1995)].
If there is no heating step, a peroxide produced by the irradiation of a polyolefin with a radiation acts as a negative charge, so that the bradykinin concentration is increased, namely, the biocompatibility is not high. Therefore, the absence of the heating step is not very desirable.
The concentration of bradykinin produced by the contact of the leukocyte-removing material of the present invention with blood is preferably low. The bradykinin concentration after the contact is preferably less than 100 times and not less than 1 time, more preferably less than 80 times and not less than 1 time, most preferably less than 60 times and not less than 1 time, as high as that before the contact.
The bradykinin concentration can easily be measured by a method such as a well-known radioimmuno-assay, enzyme immunoassay or the like.
The leukocyte-removing material of the present invention preferably has only a small amount of residual radicals after the irradiation with a radiation from the viewpoint of the stability of the material and the stability of the hydrophilicity. The amount of radicals in the polyolefin can be measured by means of an electron spin resonance (ESR) apparatus. The amount of residual radicals can be determined also by the following method: at the time of ESR measurement, manganese radicals are measured simultaneously with the measurement for the leukocyte-removing material, and there is used a radical intensity ratio obtained by dividing a maximum peak due to radicals remaining in the leukocyte-removing material by a peak due to manganese radicals.
The radical intensity ratio is preferably low because when radicals remain in the material, they deteriorate the material.
In addition, it was found that when the material is brought into contact with blood, the bradykinin concentration is increased by the contact if the radical intensity ratio is high.
The radical intensity ratio is preferably less than 1/g. When the radical intensity ratio is 1/g or more, the bradykinin concentration after the contact is undesirably 100 times or more as high as that before the contact. The radical intensity ratio is more preferably less than 0.5/g, most preferably less than 0.1/g.
The hydrophilicity of the leukocyte-removing material of the present invention is preferably invariant for a long period of time. Specifically, it is preferably stable for at least 6 months, more preferably 1 year or more, most preferably 3 years or more, under storage conditions for using the leukocyte-removing material as a medical supply.
The leukocyte-removing material of the present invention can be effectively used in a leukocyte-removing filter apparatus by packing it into a container having at least an inlet and an outlet.
When the leukocyte-removing material is used as a packing in the leukocyte-removing filter apparatus, the specification of the packing density is important because the state of pores varies depending on the packing density.
In the leukocyte-removing filter apparatus according to the present invention, the packing density is preferably less than 0.40 g/cm3 and not less than 0.01 g/cm3. When the packing density is less than 0.01 g/cm3, the frequency of contact with leukocytes is undesirably decreased. On the other hand, when the packing density is 0.40 g/cm3 or more, the pores are undesirably deformed or blocked, resulting in narrowed blood flow paths. In view of the above, the packing density is more preferably less than 0.35 g/cm3 and not less than 0.01 g/cm3, most preferably less than 0.30 g/cm3 and not less than 0.05 g/cm3.
When the leukocyte-removing material is used as a packing in the leukocyte-removing filter apparatus, a spacer material can be laminated between sheets of the leukocyte-removing material. When such a laminated structure is used, a pressure change is caused in a blood flow, resulting in aggregation and dispersion of hemocytes, and hence leukocytes can be efficiently removed.
When the leukocyte-removing material and the spacer material are laminated, they are satisfactorily laminated in a direction perpendicular to a blood flow and/or in a cylindrical form. In this case, the specification of the ratio of the leukocyte-removing material to the spacer material (hereinafter referred to as the lamination ratio) is important. The lamination ratio is calculated by the following equation.
Lamination ratio=thickness of leukocyte-removing material/thickness of spacer material
When the lamination ratio is less than 10 and not less than 0.5, an efficient pressure change is caused, so that satisfactory removal of leukocytes is possible. When the lamination ratio is less than 0.5, the amount of the leukocyte-removing material is relatively decreased, so that the size of the leukocyte-removing filter apparatus should be increased. On the other hand, when the lamination ratio is 10 or more, the thickness of the leukocyte-removing material is too large, no sufficient pressure change can be caused in a blood flow. In view of the above, the lamination ratio is more preferably less than 8 and not less than 0.5, most preferably less than 5 and not less than 0.5.
The spacer layer referred to herein is a layer in which blood flows more easily than in the leukocyte-removing material layers. As the spacer layer, there is used, for example, a wide-meshed net of metal or synthetic resin, inorganic fiber, synthetic fiber, or nonwoven fabric having an average fiber diameter larger than that of the nonwoven fabric used as the leukocyte-removing filter layers.
As the spacer material used in the leukocyte-removing filter apparatus according to the present invention, a reticular and/or woven-fabric-like material or a nonwoven-fabric-like material is satisfactorily used. The mesh size of such a spacer is preferably less than 1,000-mesh and not less than 3-mesh. When the mesh size is 1,000-mesh or more, the spacer material undesirably have too fine meshes, so that no sufficient pressure change can be caused in the flow even if the spacer material is laminated with the leukocyte-removing material. On the other hand, when the mesh size is less than 3-mesh, the leukocyte-removing material undesirably enters the meshes of the mesh material, so that no sufficient pressure change can be caused in the flow.
As a method for sterilizing the leukocyte-removing material of the present invention, well-known methods such as radiation sterilization, wet heat sterilization, chemical sterilization, etc. are used.
The leukocyte-removing material can be sterilized preferably by wet heat sterilization.
The leukocyte-removing material of the present invention is preferably sterilized in a wet state together with a filling liquid from the viewpoint of its handleability at the time of use and its stability during the sterilization. As the filling liquid, any liquid may be satisfactorily used so long as it does not deteriorate the leukocyte-removing material. The filling liquid is preferably an aqueous solution which has no undesirable influence on blood and the like even if the filling liquid remains at the time of use of the leukocyte-removing material. Particularly when leukocytes are removed from a blood component, waters such as distilled water for injection, ion-exchanged water, ultrafiltered water, etc., and aqueous solutions containing salts are preferably used.
The process for producing a hydrophilized polyolefin of the present invention is explained below. By carrying out a step of irradiating a polyolefin with a radiation in a dose of less than 300 kGy and not less than 15 kGy, and then a step of heating said material irradiated with the radiation, at a temperature of lower than 125xc2x0 C. and not lower than 75xc2x0 C., the polyolefin can be hydrophilized and can be allowed to retain hydrophilicity for a long period of time.
The irradiation of the raw material with a radiation in the presence of oxygen is preferable because it permits efficient hydrophilization. For satisfactory hydrophilization of the polyolefin, the oxygen concentration is preferably less than 100% and not less than 0.1%, more preferably less than 50% and not less than 0.1%. Therefore, the polyolefin can be efficiently hydrophilized by its irradiation in air.
In addition, the specification of the irradiation dose of the radiation is also important in suppressing the deterioration of the raw material. An irradiation dose of the radiation required for hydrophilizing the raw material is less than 300 kGy and not less than 15 kGy. When the irradiation dose of the radiation is less than 15 kGy, no sufficient hydrophilicity is undesirably attainable even if the heating step is carried out in addition to the irradiation. On the other hand, when the irradiation dose of the radiation is 300 kGy or more, the deterioration of the raw material is undesirably remarkable. The irradiation dose of the radiation is more preferably less than 200 kGy and not less than 15 kGy, most preferably less than 100 kGy and not less than 30 kGy.
As the radiation, electron beams, xcex4-rays, xcex1-rays, xcex2-rays, X-rays, etc. are used. Electron beams or xcex3-rays are preferably used form the viewpoint of the efficiency of hydrophilization. Electron beams are most preferably used from the viewpoint of the suitable transmittance of the radiation.
For the heat treatment after the irradiation, any method may be used so long as it is intended for heating. As a preferable heating method, heating at a dry state, heating in hot water, or heating in high-pressure steam is effectively employed. The heating in hot water is most preferably employed from the viewpoint of ease of operation.
The heating temperature is preferably lower than 125xc2x0 C. and not lower than 75xc2x0 C. because in this temperature range, the peroxide produced is cleaved and the amount of residual radicals can be rapidly reduced. When heating temperature is lower than 75xc2x0 C., the cleavage of the peroxide is undesirably not sufficient. In this case, when the resulting material is used as a leukocyte-removing material, the hemocompatibility is deteriorated by the residual peroxide, so that bradykinin production and the like are caused. Therefore, such a heating temperature is not desirable also from the viewpoint of biocompatibility. When the heating temperature is 125xc2x0 C. or higher, the cleavage of the peroxide is sufficient but the deterioration of the raw material is undesirably accelerated. The heating temperature should be lower than the melting point of the raw material. In view of the above, the heating temperature is more preferably lower than 125xc2x0 C. and not lower than 80xc2x0 C., most preferably lower than 121xc2x0 C. and not lower than 80xc2x0 C.
In addition, the specification of the heating time is also important. The heating time is preferably less than 200 minutes and not less than 1 minute from the viewpoint of the cleavage of the peroxide and the reduction of the amount of residual radicals. When heating time is less than 1 minute, the cleavage of the peroxide is undesirably not sufficient. When the heating is conducted for 200 minutes or more, the amount of residual radicals becomes very slight in 200 minutes. Therefore, such heating is not efficient. Thus, the heating time is more preferably less than 120 minutes and not less than 10 minutes, most preferably less than 120 minutes and not less than 15 minutes. When such a heating time is employed, the cleavage of the peroxide and the reduction of the amount of residual radicals can be efficiently achieved.
According to the process of the present invention, hydrophilicity can be efficiently imparted to a polyolefin. Since the resulting hydrophilic polyolefin is not changed in hydrophilicity over a long period of time, is hardly deteriorated as material and contains only a small amount of residual radicals and the like, it is suitably used for various purposes, in particular, medical purposes and the like.